Cultured cancer cells exhibit a much higher arginine requirement than their normal counterparts with similar growth rates. Furthermore, when arginine is omitted from the medium, or arginase added, the cancer cells die sooner than normal cells. That a reduction in the arginine content of cancerous tissue may be a first line of defense against cancer in vivo is suggested by the discovery that macrophages, which are numerous in many solid cancers, synthesize and secrete large amounts of arginase. Since most dietary proteins are rich in arginine, it follows that the removal of arginine, and its major precursors, from an amino acid diet may be effective in retarding or abolishing the growth of cancer in living animals. Furthermore, this treatment can be supplemented by the addition to the diet of canavanine, which is not only a competitive antagonist of arginine, but also a destabilizer of proteins, into which it is incorporated. In addition to these dietary approaches, we will simultaneously inject the experimental animals with homologous liver arginase; or, alternatively, with beef liver arginase whose antigenicity has been minimized by coupling with methoxypolyethylene glycol. Should arginine deprivation plus these supplementary treatments only arrest the growth of cancer cells without destroying them, a burst of mitotic activity will be produced by adding arginine to the diet and chemotherapeutic agents which are most destructive of dividing cells, such as methotrexate will be concomitantly administered. When used intermittently the latter procedure might well destroy all cancer cells, or at least minimize the often devastating effects of uninterrupted chemotherapy.